Abstract 530: A Cluster of Proteins Implicated in Kidney Disease Are Increased in HDL of Hemodialysis Subjects
Objectives: Cardiovascular disease (CVD) is the leading cause of death in uremic subjects on dialysis. However, this large increase cannot be completely explained by the conventional risk factors frequently seen in this population. One important factor could be alterations of high-density lipoprotein (HDL) protein composition that impair its cardioprotective functions. We therefore investigated alterations in the HDL proteome of end-stage renal disease (ESRD) patients undergoing hemodialysis.
Methods and Results: We first used shotgun proteomics to investigate the protein composition of HDL isolated by ultracentrifugation in 20 control and 40 ESRD subjects. This analysis identified 63 proteins in HDL, which were linked to lipid and lipoprotein metabolism, immune response, acute phase response, complement regulation, inhibitors of proteolysis, vitamin binding and transport, and platelet activation/coagulation. We then used targeted proteomics by isotope-dilution MS/MS with selected reaction monitoring (SRM) to provide precise and accurate relative quantification of 37 proteins in HDL. This quantitative approach revealed that 22 proteins (including SAA1, apoA-IV, apoC-II, apoC-III) were significantly enriched and six proteins (including apoA-I, apoA-II, PON1) were significantly decreased in ESRD patients. Moreover, several of these proteins (SAA1, apoC-III, PON1, etc.) have been associated with atherosclerosis. Strikingly, six proteins implicated in renal disease–AMBP, B2M, CFD, CST3, PTGDS and RBP4–were markedly increased in HDL of uremic subjects.
Conclusions: Our observations indicate that ESRD markedly remodels the HDL proteome. Moreover, our quantitative analysis of the HDL proteome identified a cluster of six proteins that are dramatically enriched in HDL from patients with ESRD. Our observations support the proposal that the protein cargo of HDL can serve as a marker - and perhaps mediator - of renal disease and serve as novel biomarkers for ESRD status. Therefore, quantifying proteins in HDL might help diagnose and perhaps treat human cardiovascular disease in kidney disease.
Author Disclosures: B. Shao: None. I. de Boer: None. P.S. Mayer: None. L. Zelnick: None. M. Afkarian: None. J.W. Heinecke: None. J. Himmelfarb: None.
This research has received full or partial funding support from the American Heart Association.
- © 2015 by American Heart Association, Inc.